Submissions for variant NM_033056.4(PCDH15):c.3717+2dup (rs1248401224)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000669022	SCV000793718	uncertain significance	Usher syndrome type 1F	2017-08-29	criteria provided, single submitter	clinical testing
Invitae	RCV000808578	SCV000948690	likely pathogenic	not provided	2020-01-02	criteria provided, single submitter	clinical testing	This sequence change falls in intron 27 of the PCDH15 gene. It does not directly change the encoded amino acid sequence of the PCDH15 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Usher syndrome (PMID: 22815625, 25404053). This variant is also known as c.3717+2dupTT in the literature. ClinVar contains an entry for this variant (Variation ID: 553548). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this splice site change change causes exon skipping (PMID: 23451239). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.